Safety Profile of Benznidazole in the Treatment of Chronic Chagas Disease: Experience of a Referral Centre and Systematic Literature Review with Meta-Analysis

Crespillo-Andújar, Clara; Rullo, Emmanuele Venanzi; López‐Vélez, Rogelio; Monge‐Maíllo, Begoña; Norman, Francesca; López-Polín, Ana; Pérez‐Molina, José A.

doi:10.1007/s40264-018-0696-5

Cited by 44 publications

(27 citation statements)

References 65 publications

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“…The marginal effect of treatment for adults in this phase of the disease could be due to considerable differences between studies [51][52][53][54][55]68]. While the tolerability of parasiticidal treatment is good in children, it is important to highlight the poor tolerability of treatment in adults: up to 44% of patients treated with benznidazole experience adverse effects, which have an impact on discontinuation of treatment (11% of all treated patients) [56]. The adverse effects of screening are minimal, i.e.…”

Section: Research Evidence and Remarks From The Panelmentioning

confidence: 99%

“…Furthermore, recent clinical trials on the use of imidazoles (posaconazole or ravuconazole) alone [53,54] or in combination with benznidazole [55] showed these to be less efficacious than benznidazole based on microbiological response markers (PCR for T. cruzi). A systematic review on safety of treatment showed that benznidazole was poorly tolerated, with a frequency of adverse effects of 44% and discontinuation of treatment in 11% of patients [56].…”

Section: Indication For Treatmentmentioning

confidence: 99%

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Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology

et al. 2020

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Background: Chagas disease has spread beyond its original borders on the American continent with migration. It can be transmitted from mother to child, through organ transplantation and transfusion of blood and blood products. It is necessary to determine when to screen for this infection. Aim: Our objective was to evaluate the appropriateness of screening for Trypanosoma cruzi infection in Latin American migrants and their descendants. Methods: We reviewed the literature using rigorous criteria. The quality of evidence was ranked according to the GRADE classification. An evidence to decision framework was adopted to provide information on the most relevant aspects necessary to formulate recommendations. Results: The 33 studies evaluated revealed a prevalence of T. cruzi infection among Latin American migrants in Europe of 6.08% (95% confidence interval (CI): 3.24-9.69; 28 studies). Vertical transmission occurred in three of 100 live births (95% CI: 1-6; 13 studies). The prevalence of cardiovascular disease was 19% (95% CI: 13-27; nine studies), including only 1% severe cardiac events (95% CI: 0-2; 11 studies). The overall quality of evidence was low because of risk of bias in the studies and considerable heterogeneity of the evaluated populations. The recommendations took into account economic studies on the value of screening strategies and studies on acceptability of screening and knowledge of the disease in the affected population. Conclusions: We identified five situations in which screening for T. cruzi infection is indicated. We recommend screening persons from endemic areas and children of mothers from these areas.

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Section: Research Evidence and Remarks From The Panelmentioning

confidence: 99%

Section: Indication For Treatmentmentioning

confidence: 99%

Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology

et al. 2020

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“…Cells viability was checked upon cell counting with Trypan blue staining and we only proceeded if it was >95%. Vero cells solution was diluted at a concentration of 5x10 5 6 cells per mL before adding 100 µl per well. In the case of HepG2 cells, we used a dilution of 3.2x10 4 cells per mL.…”

Section: Toxicity Assays With Vero and Hepg2 Cellsmentioning

confidence: 99%

“…But their efficacy diminishes at the chronic stage, which is usually diagnosed at adulthood with serological tests that detect specific anti-T. cruzi type G immunoglobulins (1). Moreover, both drugs 3 have long regimens of administration that entail the advent of frequent adverse events which often drive to treatment discontinuation (5)(6)(7). There is thus an urgent unmet need of safer and more efficacious drugs for the treatment of chronic Chagas disease, for which natural products may represent a promising approach to discover new lead compounds (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Martínez-Peinado

Cortes-Serra

Torras-Claveria

et al. 2020

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Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side effects and limited efficacy at the chronic stage. Natural products provide a pool of diversity structures to lead the chemical synthesis of novel molecules for this purpose. Herein we analyzed the anti- T. cruzi activity of 9 alkaloids derived from plants of the Amaryllidaceae family. Methods: the activity of each alkaloid was assessed by means of a newly developed anti- T. cruzi phenotypic assay. We further evaluated the compounds that inhibited the parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity. Results: we identified a single compound (hippeastrine 2 ) that was selectively active against the parasite yielding selectivity indexes of 12.7 and 35.2 against Vero and HepG2 cells, respectively. Conclusions: results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.

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“…Cells viability was checked upon cell counting with Trypan blue staining and we only proceeded if it was >95%. Vero cells solution was diluted at a concentration of 5x10 5 cells per mL before adding 100 µl per well. In the case of HepG2 cells, we used a dilution of 3.2x10 4 cells per mL.…”

Section: Toxicity Assays With Vero and Hepg2 Cellsmentioning

confidence: 99%

Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Martínez-Peinado

Cortes-Serra

Torras-Claveria

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side effects and limited efficacy at the chronic stage. Natural products provide a pool of diversity structures to lead the chemical synthesis of novel molecules for this purpose. Herein we analyzed the anti- T. cruzi activity of 9 alkaloids derived from plants of the Amaryllidaceae family. Methods: the activity of each alkaloid was assessed by means of an anti- T. cruzi phenotypic assay. We further evaluated the compounds that inhibited the parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity. Results: we identified a single compound (hippeastrine 2 ) that was selectively active against the parasite yielding selectivity indexes of 12.7 and 35.2 against Vero and HepG2 cells, respectively. Moreover, it showed specific activity against the amastigote stage (IC 50 = 3.31 μM). Conclusions: results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.

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Safety Profile of Benznidazole in the Treatment of Chronic Chagas Disease: Experience of a Referral Centre and Systematic Literature Review with Meta-Analysis

Abstract: Benznidazole had a poor tolerability profile, with a high incidence of TDs, especially in adult patients and women. Optimised dosing schedules and/or new drugs are urgently needed.

Cited by 44 publications

References 65 publications

Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology

Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology

Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

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